Project Summary Globally, transgender women (TW) are devastatingly burdened by HIV infection with an estimated 19.1% prevalence (meta-analysis), a nearly 50-fold increased odds of HIV relative to the general population worldwide. In Peru, TW are the most affected population, with 29.8%-48.8% HIV prevalence in the capital city of Lima, and steep increases in HIV infection rates in those ages 25 years and older. Therefore, young transgender women (YTW) ages 16-24 years constitute a critically important, yet understudied, group for early primary HIV prevention efforts. Very little is known about the mental health and psychosocial vulnerabilities (e.g., depression, posttraumatic stress disorder [PTSD], substance use disorder, gender-based violence) experienced by YTW in Peru. Concomitant mental health and other psychosocial health conditions resulting from stigma, and during the critical developmental period of late adolescence and young adulthood, may synergistically potentiate risk for HIV for YTW in Peru, and influence biobehavioral HIV prevention targets like protected sex, sterile needle injecting practices, and pre-exposure prophylaxis (PrEP) uptake. Guided by a psychosocial syndemics framework and Lifecourse Health Development model, the goal of this study is to: a) characterize the prevalence, distribution, and correlates of HIV infection and related STI co-infections in YTW ages 16-24 years in Lima, Peru, and b) assess co-occurring mental health and psychosocial conditions (vulnerabilities and resiliencies) and their influence on HIV transmission risk. In Aim 1, we will conduct formative in-depth interviews to understand developmental and psychosocial contexts of HIV risk for YTW in Peru. We will also gather data on perceived acceptability and barriers/ facilitators to social network-based recruitment methods. In Aim 2, we will characterize the prevalence, distribution, and correlates of HIV and STI- coinfections, and multiple stigma-related health conditions (e.g., depression, PTSD, substance use disorder, bullying, family rejection) in a sample of 400 YTW recruited via social network-based methods. We will characterize the acceptability and rates of recruitment to inform future HIV prevention trials. In Aim 3, we will test several statistical approaches to modeling co-occurring syndemic risk factors in YTW, and simultaneously consider: the extent to which conditions in the aggregate are associated with HIV risk; the extent to which conditions interact to intensify HIV risk. Reducing HIV disparities for transgender populations in Peru will require reaching YTW ages 16-24 years for early HIV prevention. This study will increase scientific knowledge of the multiple mental health and psychosocial intersecting epidemics fueling HIV risk and STI co-morbidities in YTW. Findings will inform the design and implementation of biobehavioral HIV prevention interventions for YTW in Peru, such as those which target developmentally-specific clusters of stigma-related conditions, to maximize impact on the HIV epidemic and decrease HIV burden among TW globally. Findings can also be used to inform early HIV prevention efforts for Latina/ Hispanic YTW in the U.S.